Dermatophyte infections are not only a major cause of morbidity, stress, aggravation and economic (time and productivity) loss for the American population, but they are also very interesting and unique from the standpoint of host-parasite relationships and immunity to infectious (and possibly neoplastic) disease. This research program will use germfree guinea pigs and nude mice to elucidate the innate and/or acquired immune mechanism(s) employed by the host to curtail, prevent or eliminate infectious fungi from dead (stratum corneum and hair) keratinized tissues. Over 60 years of research on immunity to dermatophytes has failed to answer many basic questions on the relative importance of innate and acquired immunity to these pathogenic fungi. The lack of a dermatophyte-free model has caused much contradictory and even nonreproducible data to appear in the literature. Our proposal to utilize germfree guinea pigs and nude mice to study the basic host-parasite interactions, the temporal aspects of the infection, and the immune mechanism (i.e., innate, antibody, or thymus-dependent cell-mediated) that are responsible for the prevention and/or control of dermatophyte infections are a unique approach to studies on immunity and pathogenesis of the dermatophytoses. Because of their lack of exposure to viable fungi, true, uncluttered information on the infectious and immune aspects of dermatophyte infections will be the result of this study with gnotobiotic models. Once elucidated, the mechanism(s) employed by the host to control an infection in stratum corneum or hair (immunologically privileged sites) would add basic new information to our knowledge of infectious disease immunology.